A 52-year-old, HIV-positive man presents with a several-month history of penile lesions. The sites are moderately tender. Current medications include etravirine, ritonavir, darunavir, and emtricitabine/tenofovir. Culture was positive for herpes simplex, but the condition has persisted despite topical treatment with acyclovir ointment and oral acyclovir.
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The herpes simplex viruses comprise 2 types of DNA viruses: herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2). HSV-1 causes oral lesions in approximately 80% of cases and genital lesions in 20% of cases. The opposite is true of HSV-2, which causes genital lesions in approximately 80% of cases and oral lesions in 20%.
Primary infections are generally mild and asymptomatic; however, severe infections involving multiple organ systems may develop in those with immunocompromise. After the person’s body begins to produce antibodies, the infection becomes latent in the sensory ganglia. The viruses become reactivated secondary to certain stimuli, including fever, physical or emotional stress, ultraviolet light exposure, and axonal injury.1
In the United States, approximately 80% of adults have antibodies to HSV-1, whereas antibodies to HSV-2 are found in approximately 20% of the population. The incidence of genital herpes has been estimated to be 500,000 to 1,000,000 cases per year, with a prevalence of 40 to 60 million individuals affected. African-Americans are more likely to be infected with HSV-2 than any other racial or ethnic group.2 HSV-2 antibodies are present in approximately 20% of white adults and in approximately 65% of African-American adults.1
HSV-1 infections are spread through respiratory droplets or direct exposure to infected saliva. HSV-2 is generally transferred by means of genital contact involving mucous membranes or damaged skin. The incubation period for HSV-2 is from 2 to 12 days, and vesicles typically erupt 6 to 48 hours after the onset of a prodrome. Herpes viruses cause cytolytic infections, and therefore, pathologic changes are caused by cell necrosis as well as by inflammatory changes. The virus travels from the site of infection in the skin or mucosa to the sensory dorsal root and remains latent until a recurrent outbreak.1
The 2006 Centers for Disease Control guidelines for sexually transmitted diseases recommend treatment of all initial genital herpes infections with antiviral medications to reduce potential complications.3 Acyclovir provides initial, recurrent, and suppressive therapy for genital HSV. Daily suppressive therapy has been shown to be 80% effective in preventing reappearance of HSV and should be considered in those who have frequent recurrences.4 If lesions persist or recur in a person receiving antiviral treatment, HSV resistance should be suspected and a viral isolate should be obtained for sensitivity testing.5 All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir. Foscarnet (40-80 mg/kg intravenously every 8 hours until clinical resolution is attained) is often effective for treatment of acyclovir-resistant genital herpes.6,7 Intravenous cidofovir 5 mg/kg once weekly might also be effective, and topical imiquimod and cidofovir 1% gel are also alternatives.8,9
The prevalence of acyclovir-resistant isolates has remained stable at approximately 3% among those who are immunocompromised. Only 3 cases of clinical resistance of HSV to acyclovir have been reported. However, the incidence in those with immunocompromise, particularly those with AIDS and those who have undergone bone marrow transplant, is increasing.10
Michael Stas, DPM, is a podiatry-dermatology fellow at St. Luke’s University Hospital in Bethlehem, Pennsylvania, and at the DermDox Dermatology Center in Hazleton, Pennsylvania. Stephen Schleicher, MD, is an associate professor of medicine at the Commonwealth Medical College in Scranton, Pennsylvania, and an adjunct assistant professor of dermatology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. He practices dermatology in Hazleton, Pennsylvania.
- Sharma R. Herpes simplex in emergency medicine. Medscape. http://emedicine.medscape.com/article/783113-overview. Updated October 27, 2015. Accessed September 22, 2016.
- Biggs WS, Williams RM. Common gynecologic infections. Prim Care. 2009;36:33-51, viii.
- Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55:1-94.
- Frenkl TL, Potts J. Sexually transmitted infections. Urol Clin North Am. 2008;35:33-46; vi.
- Reyes M, Shaik NS, Graber JM, et al; Task Force on Herpes Simplex Virus Resistance. Acyclovir-resistant genital herpes among persons attending sexually transmitted disease and human immunodeficiency virus clinics. Arch Intern Med. 2003;163:76-80.
- Safrin S, Crumpacker C, Chatis P, et al. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. N Engl J Med. 1991;325:551-555.
- Levin MJ, Bacon TH, Leary JJ. Resistance of herpes simplex virus infections to nucleoside analogues in HIV-infected patients. Clin Infect Dis. 2004;39(Suppl 5):S248-S257.
- Perkins N, Nisbet M, Thomas M. Topical imiquimod treatment of aciclovir-resistant herpes simplex disease: case series and literature review. Sex Transm Infect. 2011;87:292-295.
- McElhiney LF. Topical cidofovir for treatment of resistant viral infections. Int J Pharm Compd. 2006;10:324-328.
- Portage JC Jr, Kessler HA. Herpes simplex virus resistance to acyclovir: clinical relevance. Infect Agents Dis. 1995,4:115-124.